TY - JOUR
T1 - Regulation of growth inhibitory activity in transformed mouse embryo fibroblasts
AU - Levine, Alan E.
AU - Crandall, Craig A.
AU - Brattain, Michael G.
N1 - Funding Information:
The authors thank B. Young and S. E. Kim for excellent technical assistance and Dr. K. Stromberg of the Frederick Cancer Research Facility for the generous gift of ‘“I-labeled TGF-& This research was supported by American Cancer Society Grant BC-492 and NIH Grant CA38100 to A.E.L. and by NIH Grants CA34432 and CA38173 to M.G.B.
PY - 1987/8
Y1 - 1987/8
N2 - Treatment of the transformed mouse embryo fibroblast cell line AKR-MCA with 1% N, N-dimethylformamide (DMF) resulted in the restoration of a nontransformed phenotype in these cells. In order to determine if an increase in growth inhibitory peptides might be responsible for these changes in growth properties of the DMF-treated AKR-MCA cells we examined the serum-free conditioned medium for its ability to inhibit the anchorage-independent growth of a human colon carcinoma cell line. The extracellular levels of inhibitory activity were two-fold higher in conditioned medium derived from AKR-MCA cells than in AKR-MCA cells grown in 1% DMF (AKR-MCA/DMF). Fractionation of the crude conditioned medium indicated the presence of an Mr 20,000 inhibitory fraction in AKR-MCA/DMF conditioned medium which was reduced in AKR-MCA cells. This Mr, 20,000 inhibitory activity was acid and heat stable and sensitive to dithiothreitol and trypsin. In addition to inhibiting the growth of a human colon carcinoma cell line this protein induced colony formation in AKR-2B cells and competed for binding to the transforming growth factor β (TGF-β) receptor. Therefore, this Mr, 20,000 inhibitory polypeptide induced by DMF is probably TGF-β. TGF-β was also shown to inhibit the growth of AKR-MCA cells in monolayer culture.
AB - Treatment of the transformed mouse embryo fibroblast cell line AKR-MCA with 1% N, N-dimethylformamide (DMF) resulted in the restoration of a nontransformed phenotype in these cells. In order to determine if an increase in growth inhibitory peptides might be responsible for these changes in growth properties of the DMF-treated AKR-MCA cells we examined the serum-free conditioned medium for its ability to inhibit the anchorage-independent growth of a human colon carcinoma cell line. The extracellular levels of inhibitory activity were two-fold higher in conditioned medium derived from AKR-MCA cells than in AKR-MCA cells grown in 1% DMF (AKR-MCA/DMF). Fractionation of the crude conditioned medium indicated the presence of an Mr 20,000 inhibitory fraction in AKR-MCA/DMF conditioned medium which was reduced in AKR-MCA cells. This Mr, 20,000 inhibitory activity was acid and heat stable and sensitive to dithiothreitol and trypsin. In addition to inhibiting the growth of a human colon carcinoma cell line this protein induced colony formation in AKR-2B cells and competed for binding to the transforming growth factor β (TGF-β) receptor. Therefore, this Mr, 20,000 inhibitory polypeptide induced by DMF is probably TGF-β. TGF-β was also shown to inhibit the growth of AKR-MCA cells in monolayer culture.
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U2 - 10.1016/0014-4827(87)90168-6
DO - 10.1016/0014-4827(87)90168-6
M3 - Article
C2 - 2887448
AN - SCOPUS:0023470594
VL - 171
SP - 357
EP - 366
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 2
ER -